The aim of this study was to determine health care resource utilization and direct medical costs in Spanish patients treated with intravenous immunoglobulins (IVIGs) in 2009. Cost-of-illness analyses were performed to estimate direct medical costs of patients treated with IVIGs. Prevalence data were obtained from the Spanish Primary Immunodeficiency registry. A semi-structured questionnaire was used to collect data on health care resource utilization and patient distribution. Drug, administration, and premedication costs were considered from the payer's perspective. Separate analyses were conducted for children and adolescents versus adults. The numbers of children and adolescents with replacement therapy were 724, with immunomodulation 243, and with allogeneic bone marrow transplantation 30. The numbers of adult patients were, respectively, 3450, 1134, and 172. Mean annual costs for children and adolescents were 6293 € with Privigen, 6292 € with Kiovig, 6939 € with Flebogamma, and 6559 € with Octagamocta. For adults, estimations were 17 106 € with Privigen, 17 103 € with Kiovig, 18 077 € with Flebogamma, and 17 423 € with Octagamocta. Direct medical costs for IVIGs were approximately 91.8 million €. Drug costs represented 94% of total costs. The choice for a certain IVIG treatment depends on individual patient characteristics and cost considerations.